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Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences

Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and o...

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Detalles Bibliográficos
Autores principales: Ramikie, Teniel S., Ressler, Kerry J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Les Laboratoires Servier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286726/
https://www.ncbi.nlm.nih.gov/pubmed/28179812
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author Ramikie, Teniel S.
Ressler, Kerry J.
author_facet Ramikie, Teniel S.
Ressler, Kerry J.
author_sort Ramikie, Teniel S.
collection PubMed
description Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other stress-related disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species. Moreover, increasing evidence suggests that this pathway is regulated by both stress and estrogen modulation and may provide an important window into understanding mechanisms of sex differences in the stress response. We have recently shown that PACAP and its receptor (PAC1R) are critical mediators of abnormal processes after psychological trauma. Notably, in heavily traumatized human subjects, there appears to be a robust sex-specific association of PACAP blood levels and PAC1R gene variants with fear physiology, PTSD diagnosis, and symptoms, specifically in females. The sex-specific association occurs within a single-nucleotide polymorphism (rs2267735) that resides in a putative estrogen response element involved in PAC1R gene regulation. Complementing these human data, the PAC1R messenger RNA is induced with fear conditioning or estrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD.
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spelling pubmed-52867262017-02-08 Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences Ramikie, Teniel S. Ressler, Kerry J. Dialogues Clin Neurosci Translational Research Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other stress-related disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species. Moreover, increasing evidence suggests that this pathway is regulated by both stress and estrogen modulation and may provide an important window into understanding mechanisms of sex differences in the stress response. We have recently shown that PACAP and its receptor (PAC1R) are critical mediators of abnormal processes after psychological trauma. Notably, in heavily traumatized human subjects, there appears to be a robust sex-specific association of PACAP blood levels and PAC1R gene variants with fear physiology, PTSD diagnosis, and symptoms, specifically in females. The sex-specific association occurs within a single-nucleotide polymorphism (rs2267735) that resides in a putative estrogen response element involved in PAC1R gene regulation. Complementing these human data, the PAC1R messenger RNA is induced with fear conditioning or estrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD. Les Laboratoires Servier 2016-12 /pmc/articles/PMC5286726/ /pubmed/28179812 Text en Copyright: © 2016 Institut la Conference Hippocrate - Servier Research Group http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Translational Research
Ramikie, Teniel S.
Ressler, Kerry J.
Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title_full Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title_fullStr Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title_full_unstemmed Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title_short Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences
title_sort stress-related disorders, pituitary adenylate cyclase—activating peptide (pacap)ergic system, and sex differences
topic Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286726/
https://www.ncbi.nlm.nih.gov/pubmed/28179812
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